President Obama and European leaders called Thursday for Syrian President Bashar al-Assad to resign, after months of his violent crackdown on protesters. The rhetorical escalation was backed by new U.S. sanctions designed to undermine Assad’s ability to finance his military operation.

“The future of Syria must be determined by its people, but President Bashar al-Assad is standing in their way,” Obama said in a written statement. “For the sake of the Syrian people, the time has come for President Assad to step aside.”

Obama’s first explicit call for Assad to resign — something critics have pressured him to do — culminated months of calibrated diplomacy that has included three rounds of sanctions and a gradual policy shift toward regime change in a nation long at odds with U.S. policy in the Middle East.

The president made his announcement hours before leaving on a 10-day vacation at Martha’s Vineyard, where he has little contact with journalists, and as Assad presses ahead with a broad military campaign that has killed hundreds of Syrian civilians. The crackdown is one of the most brutal government responses to protests during the tumultuous Arab Spring.

As Obama issued his statement, the leaders of France, Germany and Britain joined him in calling on Assad “to face the reality of the complete rejection of his regime by the Syrian people and to step aside.”

Obama had spoken to French President Nicolas Sarkozy, German Chancellor Angela Merkel and British Prime Minister David Cameron over the past two weeks to discuss calling for Assad’s resignation and to coordinate steps on sanctions.

Many of Obama’s critics, including Senate hawks and human rights groups, questioned his reluctance to call for Assad’s ouster, a move opposed until recently by key regional U.S. allies such as Turkey and Saudi Arabia. The critics have compared it unfavorably to Obama’s more rapid decision to end support for now-ousted Egyptian President Hosni Mubarak, a longtime U.S. ally.

Human rights advocates estimate that more than 2,000 Syrian civilians have been killed in the Assad government’s five-month-old crackdown, which has spread from restive border areas in the south to many of the country’s major cities.

On Thursday, the top U.N. human rights agency issued a scathing account of the operation, urging the Security Council to consider authorizing the International Criminal Court to investigate possible crimes against humanity. Several Western nations also plan to draft a U.N. resolution that would demand that Syria stop its crackdown and would impose an arms embargo on Damascus.

Syria’s U.N. ambassador, Bashar al-Jaafari, said the United States “is launching a humanitarian and diplomatic war against us.”

The sanctions that the Obama administration announced Thursday freeze all Syrian government assets that are under U.S. jurisdiction and bar Americans from doing business with the government.

They also prohibit the import of Syrian oil and petroleum products, an essential element of Syria’s economy, to the United States. Diplomats said European leaders, whose countries consume about 90 percent of Syria’s petroleum exports, were exploring similar curbs.

In Washington, senior administration officials said Assad’s escalation of violence since the start of the Muslim holy month of Ramadan, coupled with the recent failure of Turkish-led diplomatic efforts to persuade him to end his military campaign, prompted the harsher sanctions and rhetoric.

This month, the six Arab nations of the Gulf Cooperation Council also condemned Assad’s campaign and called for “an immediate end to violence.” For months, U.S. officials have said that they want to echo, rather than preempt, Arab sentiment regarding Assad to avoid undermining opposition to Syria’s government in a region where Western motives are viewed with suspicion.

The White House decided last week to issue its call for Assad’s departure amid a surge of diplomatic efforts to coordinate its response with allies. “Even if no one else would have joined us, we were still ready to do it,” said a senior administration official, who spoke on the condition of anonymity to describe internal policy discussions.

But as the White House began notifying allies, Turkey asked for a delay, dispatching Foreign Minister Ahmet Davutoglu to Damascus to make a final appeal to Assad. The Syrian leader soon after sent troops and tanks into the coastal town of Latakia, killing protesters there.

Turkey did not join in the calls for Assad’s ouster. But Turkish Prime Minister Recep Tayyip Erdogan conferred by telephone with Obama and criticized Assad, comparing his behavior to that of Libyan leader Moammar Gaddafi.

At the State Department, Secretary of State Hillary Rodham Clinton said the sanctions would “strike at the heart of the regime” by depriving it of the hard currency needed to finance its security forces.

A second senior administration official said the White House is “certain Assad is on his way out,” calling the protests a sign that Syria is “emerging from what in effect has been 40 years of an induced political coma.”

“They’re not afraid anymore,” the official said, referring to ordinary Syrians. “And that’s when regimes start to crumble and transitions begin.”

“Obviously Assad isn’t going to stop shooting and step down simply because the international community tells him to,” said Tom Malinowski, the Washington director of Human Rights Watch. “The point of these kinds of measures is to diminish the legitimacy of the regime and to boost that of the activists on the street, increasing the chance that those on the fence will get on the right side of history.”

What would follow the Assad government — a family franchise in place for more than four decades — also remains uncertain. Assad and his late father, Hafez, who preceded him as president, are from the Alawite sect of Islam, a minority in Syria that has benefited greatly over the decades at the expense of the majority Sunni Muslim population.

Some U.S. allies in the region worry that Assad could be toppled in an Alawite-led coup designed to preserve those political and economic privileges, resulting in neither meaningful change nor peace. The Sunni majority, however, has an Islamist strain long repressed by the Assads that could demand a larger role in the next government.

Until now, many Syrians have interpreted the world’s response as tacit support for Assad, leaving them reluctant to turn against the government. But activists said they hoped Obama’s statement would energize a movement that had begun to flag in the face of the military crackdown.

“It will encourage people that the international community is moving faster against the regime, and it will give us hope,” said Amer al-Sadeq, a Damascus-based organizer in the Syrian Revolution Coordinators Union, one of the bigger groups organizing the largely spontaneous protests.

The hope is that the “silent majority,” notably in Damascus and Aleppo, the two largest cities yet to experience large-scale protests, will declare its opposition to the regime, said another Damascus-based activist, who spoke on the condition of anonymity for security reasons.

“With what Obama said, it’s going to become widespread now,” the activist said. “I think we’re going to see lots of people taking to the streets.”

Correspondents Liz Sly in Beirut and Colum Lynch at the United Nations contributed to this report.